1Q3P

Crystal structure of the Shank PDZ-ligand complex reveals a class I PDZ interaction and a novel PDZ-PDZ dimerization

Summary for 1Q3P

• Entry DOI: 10.2210/pdb1q3p/pdb
• Related: 1Q3O
• Descriptor: Shank1, C-terminal hexapeptide from Guanylate kinase-associated protein (3 entities in total)
• Functional Keywords: shank, pdz, gkap, peptide binding protein
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cytoplasm: Q9WV48
• Total number of polymer chains: 4
• Total formula weight: 25583.50

Authors

Im, Y.J.,Lee, J.H.,Park, S.H.,Park, S.J.,Rho, S.-H.,Kang, G.B.,Kim, E.,Eom, S.H. (deposition date: 2003-07-31, release date: 2004-01-27, Last modification date: 2023-10-25)

Primary citation

Im, Y.J.,Lee, J.H.,Park, S.H.,Park, S.J.,Rho, S.-H.,Kang, G.B.,Kim, E.,Eom, S.H.
Crystal structure of the Shank PDZ-ligand complex reveals a class I PDZ interaction and a novel PDZ-PDZ dimerization
J.Biol.Chem., 278:48099-48104, 2003

PubMed Abstract: The Shank/proline-rich synapse-associated protein family of multidomain proteins is known to play an important role in the organization of synaptic multiprotein complexes. For instance, the Shank PDZ domain binds to the C termini of guanylate kinase-associated proteins, which in turn interact with the guanylate kinase domain of postsynaptic density-95 scaffolding proteins. Here we describe the crystal structures of Shank1 PDZ in its peptide free form and in complex with the C-terminal hexapeptide (EAQTRL) of guanylate kinase-associated protein (GKAP1a) determined at 1.8- and 2.25-A resolutions, respectively. The structure shows the typical class I PDZ interaction of PDZ-peptide complex with the consensus sequence -X-(Thr/Ser)-X-Leu. In addition, Asp-634 within the Shank1 PDZ domain recognizes the positively charged Arg at -1 position and hydrogen bonds, and salt bridges between Arg-607 and the side chains of the ligand at -3 and -5 positions contribute further to the recognition of the peptide ligand. Remarkably, whether free or complexed, Shank1 PDZ domains form dimers with a conserved beta B/beta C loop and N-terminal beta A strands, suggesting a novel model of PDZ-PDZ homodimerization. This implies that antiparallel dimerization through the N-terminal beta A strands could be a common configuration among PDZ dimers. Within the dimeric structure, the two-peptide binding sites are arranged so that the N termini of the bound peptide ligands are in close proximity and oriented toward the 2-fold axis of the dimer. This configuration may provide a means of facilitating dimeric organization of PDZ-target assemblies.

PubMed: 12954649
DOI: 10.1074/jbc.M306919200

Experimental method

X-RAY DIFFRACTION (2.25 Å)